Effect of anti-luteinizing hormone antibodies on the gonadotropic cells of the pituitary in immature male rats: an electron microscopic study.

Treatment of immature rats with antigonadotropic serum results in atrophy of gonads and castration-like changes of gonadotroph cells in the pituitary gland. Newborn male albino Wistar rats were daily and subcutaneously inoculated with 0.1 to 0.8 ml of anti-luteinizing hormone (LH) sera from the first 24 hours of age, through the first 5 weeks. For controls, a similar schedule with normal rabbit serum was used. Rats were killed at weekly intervals and pituitaries were fixed for electron microscopy. The anti-LH titer, determined by microhemagglutination, was between 1:2, 560 and 1:10,240; the greatest contaminant was follicle-stimulating hormone, with the antiserum ranging from 1:160 to 1:320. Absorbed antisera, checked by double agar diffusion against unabsorbed antisera, showed no precipitin lines, indicating no antigen excess. There was no significant cytologic difference between control and experimental pituitaries during the 1st week of treatment. At the end of the 2nd week, gonadotroph cells contained a highly developed Golgi complex; by the 3rd week these cells contained pronounced, dilated, saclike ergastoplasmic cisternae, with few secretory granules in the cytoplasm of one type; by the 4th week, ergastoplasmic cisternae had broken down to form the first large vacuoles of "castration" LH gonadotrophs, some of which contained typical granules. Numerous mitotic and chromophobe cells were also observed. At the end of the 5th week castration LH cells persisted, in addition to mitotic cells, chromophobes, and numerous follicle-stimulating hormone gonadotrophs with degenerated features. The effect of anti-LH antisera on pituitary gonadotrophs could be explained as a neutralization of endogenous LH, probably not only inhibiting the long feedback mechanism, but also the short feedback loop at the level of the same pituitary cells.

[Cytological changes in hypophysis of immatur rats after administration of anti-LH antibodies (author's transl)]. / Cambios en la citología hipofisaria de ratas inmaduras por administración de anticuerpos anti-LH

In the present work, cytological changes produced in rats' pars distalis were studied by administration of anti-LH antibodies. The anti-LH sera was obtained by active immunization of adult rabbits using bovine LH hormone with Freund's complete adjuvant. Newborn albino Wistar male and female rats were daily and subcutaneously inoculated with 0.1 ml. to 0.8 ml of anti-LH sera from the first 24 hr. on during 5 weeks. For controls, a similar schedule of inoculations with normal rabbit serum was used. At weekly intervals during the treatment, 5 lots of rats were sacrificed and the rest after a recovery period of 95 days. At the end of the 2nd week of immunization, both male and female animals showed degranulated gonadotroph cells in the central part of the pars distalis; at the 3rd week these cells were hypertrophied and presented developed Golgi complex. At the 4th week, the first large vacuoles of "castration" were seen in the gonadotroph cells of male pars distalis, besides in the females the degranulation of gonadotrophs continued. During the last week of treatment, the gonadotrophs of the male animals presented a highly dilated Golgi complex, more "castration-like cells" and numerous mitosis figures. The gonadotrophs of females pars distalis presented degranulation, but not vacuoles. After the recovery period the gonadotrophs of male rats were similar to those of the control hypophisis and did not show castration vacuoles in their cytoplasm. In female rats, the gonadotrophic cells showed "castration-like vacuoles" and a raised number of mitosis cells compared to control pituitaries. The significance of these findings will be discussed.